This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Serunian, L A Articles by Cantley, L C Search for Related Content PubMed PubMed Citation Articles by Serunian, L A Articles by Cantley, L C

 Previous Article  |  Next Article 

J Virol. 1990 October; 64(10): 4718-4725

Production of novel polyphosphoinositides in vivo is linked to cell transformation by polyomavirus middle T antigen.

Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.

ABSTRACT

Phosphatidylinositol 3-kinase associates with the polyomavirus middle T antigen (PyMTAg)-pp60c-src complex in polyomavirus-transformed cells. Here we show that anti-PyMTAg immunoprecipitates from PyMTAg-transformed NIH 3T3 cells have lipid kinase activities that phosphorylate phosphatidylinositol, phosphatidylinositol-4-bisphosphate, and phosphatidylinositol-4,5-bisphosphate at the D-3 position of the inositol ring to produce three new polyphosphoinositides: phosphatidylinositol-3-phosphate (PI-3-P), phosphatidylinositol-3,4-bisphosphate (PI-3,4-P2), and phosphatidylinositol trisphosphate (PIP3), respectively. PI-3-P was detected in intact parental and PyMTAg-transformed NIH 3T3 fibroblasts at both low and high cell densities. However, parental NIH 3T3 fibroblasts produced no detectable PI-3,4-P2 or PIP3 at high density. In contrast, growing, subconfluent cells and wild-type PyMTAg-transformed cells at high density had greatly enhanced incorporation of [3H]-inositol into these highly phosphorylated lipids. Cells transfected with a transformation-defective mutant of PyMTAg had undetectable levels of PI-3,4-P2 and PIP3 at high density. Thus, the synthesis of novel polyphosphoinositides by lipid kinase activity associated with PyMTAg correlates with cell growth and transformation.

This article has been cited by other articles:

• Maglione, J. E., McGoldrick, E. T., Young, L. J.T., Namba, R., Gregg, J. P., Liu, L., Moghanaki, D., Ellies, L. G., Borowsky, A. D., Cardiff, R. D., MacLeod, C. L. (2004). Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: Single origin, divergent evolution, and multiple outcomes. Molecular Cancer Therapeutics 3: 941-953 [Abstract] [Full Text]  
• Gottlieb, K. A., Villarreal, L. P. (2001). Natural Biology of Polyomavirus Middle T Antigen. Microbiol. Mol. Biol. Rev. 65: 288-318 [Abstract] [Full Text]  
• Qian, W., Wiman, K. G. (2000). Polyoma Virus Middle T and Small t Antigens Cooperate to Antagonize p53-induced Cell Cycle Arrest and Apoptosis. Cell Growth Differ. 11: 31-39 [Abstract] [Full Text]  
• Cantley, L. C., Neel, B. G. (1999). New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. USA 96: 4240-4245 [Abstract] [Full Text]  
• Beslu, N., LaRose, J., Casteran, N., Birnbaum, D., Lecocq, E., Dubreuil, P., Rottapel, R. (1996). Phosphatidylinositol-3' Kinase Is Not Required for Mitogenesis or Internalization of the Flt3/Flk2 Receptor Tyrosine Kinase. J. Biol. Chem. 271: 20075-20081 [Abstract] [Full Text]  
• Wang, J., Auger, K. R., Jarvis, L., Shi, Y., Roberts, T. M. (1995). Direct Association of Grb2 with the p85 Subunit of Phosphatidylinositol 3-Kinase. J. Biol. Chem. 270: 12774-12780 [Abstract] [Full Text]  
• Soltoff, S.P., Carpenter, C.L., Auger, K.R., Kapeller, R., Schaffhausen, B., Cantley, L.C. (1992). Phosphatidylinositol-3 Kinase and Growth Regulation. Cold Spring Harb Symp Quant Biol 57: 75-80 [Abstract]